@article{0b82e9c787a24128abf05edc51c08911,
title = "ERG cooperates with androgen receptor in regulating trefoil factor 3 in prostate cancer disease progression",
abstract = "To elucidate the role of ETS gene fusions in castration-resistant prostate cancer (CRPC), we characterized the transcriptome of 54 CRPC tumor samples from men with locally advanced or metastatic disease. Trefoil factor 3 (TFF3) emerged as the most highly differentially regulated gene with respect to ERG rearrangement status and resistance to hor-moneablation therapy. Conventional chromatin immunoprecipitation (ChIP)-polymerase chain reaction and ChIP followed by DNA sequencing (ChIP-seq) revealed direct binding of ERG to ETS binding sites in the TFF3 promoter in ERG-rearranged prostate cancer cell lines. These results were confirmed in ERG-rearranged hormone-naive prostate cancer (HNPC) and CRPC tissue samples. Functional studies demonstrated that ERG has an inhibitory effect on TFF3 expression in hormone-naive cancer but not in the castration-resistant state. In addition, we provide evidence suggesting an effect of androgen receptor signaling on ERG-regulated TFF3 expression. Furthermore, TFF3 overexpression enhances ERG-mediated cell invasion in CRPC prostate cancer cells. Taken together, our findings reveal a novel mechanism for enhanced tumor cell aggressiveness resulting from ERG rearrangement in the castration-resistant setting through TFF3 gene expression.",
author = "Rickman, {David S.} and Chen, {Ying bei} and Samprit Banerjee and Yihang Pan and Jindan Yu and Terry Vuong and Sven Perner and Lafargue, {Christopher J.} and Mertz, {Kirsten D.} and Setlur, {Sunita R.} and Kanishka Sircar and Chinnaiyan, {Arul M.} and Bismar, {Tarek A.} and Rubin, {Mark A.} and Francesca Demichelis",
note = "Funding Information: Address all correspondence to: Francesca Demichelis, PhD, Department of Pathology and Laboratory Medicine, Institute for Computational Biomedicine, Weill Cornell Medical College, 1305 York Ave, Y 1307 (or Box 140), New York, NY 10065. E-mail: frd2004@med.cornell.edu 1This study was funded by the Department of Defense New Investigator Award PC081337 (D.S.R.), the National Cancer Institute R01 CA125612-01 (F.D. and M.A.R.), the Prostate Cancer Canada, and The Young Investigator Award of the Prostate Cancer Foundation, USA (T.A.B.). 2S. Perner, A. M. Chinnaiyan, M. A. Rubin, and F. Demichelis are coinventors on a patent filed by The University of Michigan and The Brigham and Women{\textquoteright}s Hospital covering the diagnostic and therapeutic fields for ETS fusions in prostate cancer. The diagnostic field has been licensed to Gen-Probe, Inc. 3This article refers to supplementary materials, which are designated by Tables W1 and W2 and Figures W1 to W3 and are available online at www.neoplasia.com. 4These authors equally contributed to this study. 5These authors share the senior authorship. Received 18 June 2010; Revised 17 August 2010; Accepted 24 August 2010 Copyright {\textcopyright} 2010 Neoplasia Press, Inc. All rights reserved 1522-8002/10/$25.00 DOI 10.1593/neo.10866",
year = "2010",
month = dec,
doi = "10.1593/neo.10866",
language = "English (US)",
volume = "12",
pages = "1031--1040",
journal = "Neoplasia",
issn = "1522-8002",
publisher = "Elsevier Inc.",
number = "12",
}